title: Acetylome and phosphoproteome modifications in imatinib resistant chronic myeloid leukaemia cells treated with valproic acid.
abstract: Chronic myeloid leukaemia has a specific therapy: BCR/ABL inhibitor imatinib. Resistance due to BCR/ABL dependent and independent mechanisms is partially reversible by histone deacetylase inhibitors. We analysed by 2D-electrophoresis and anti-pan-acetylated and anti-phosphotyrosine immunoblots, followed by spot-matching and MALDI-TOF mass spectrometry, which proteome modifications would parallel restoration of sensitivity to imatinib by valproic acid (VPA). VPA plus imatinib significantly increased acetylation of HSP90 and hnRNP L and decreased phosphorylation of HSPs and hnRNPs in imatinib resistant cells. VPA was able to modify profoundly acetylome and phosphoproteome of CML cells, while reverting resistance to imatinib.
authors.affiliation: Functional Unit of Haematology, Department of Experimental Pathology and Oncology, University of Florence, Florence, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Buchi
authors.forename: Roberta
authors.initials: R
authors.lastname: Pastorelli
authors.forename: Germano
authors.initials: G
authors.lastname: Ferrari
authors.forename: Elena
authors.initials: E
authors.lastname: Spinelli
authors.forename: Antonella
authors.initials: A
authors.lastname: Gozzini
authors.forename: Francesca
authors.initials: F
authors.lastname: Sassolini
authors.forename: Alberto
authors.initials: A
authors.lastname: Bosi
authors.forename: Donatella
authors.initials: D
authors.lastname: Tombaccini
authors.forename: Valeria
authors.initials: V
authors.lastname: Santini
mesh_terms: D000107:Acetylation; D017209:Apoptosis; D001549:Benzamides; D015153:Blotting, Western; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm; D015180:Electrophoresis, Gel, Two-Dimensional; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006801:Humans; D000068877:Imatinib Mesylate; D047468:Immunoprecipitation; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000378:metabolism*; D019000:Phosphotyrosine / Q000378:metabolism*; D010879:Piperazines / Q000009:adverse effects*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects; D020543:Proteome / Q000032:analysis*; D011743:Pyrimidines / Q000009:adverse effects*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014407:Tumor Cells, Cultured; D014635:Valproic Acid / Q000627:therapeutic use*
chemical_list: D001549:Benzamides; D056572:Histone Deacetylase Inhibitors; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D020543:Proteome; D011743:Pyrimidines; D012333:RNA, Messenger; D019000:Phosphotyrosine; D014635:Valproic Acid; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl